Our objectives are to learn how the cardiorespiratory system normally couples to cell metabolism during exercise and how the coupling is modified by disease states. We aim to: 1) describe the gas exchange responses to exercise and recovery and how the components of the cardiorespiratory system interact to meet the cellular gas exchange needs, 2) demonstrate how disease states disrupt the normal coupling between external and internal respiration during exercise and how this information can be used, diagnostically, 3) develop the clinical applications of the anaerobic threshold, 4) compare metabolic markers of the cell redox state to the continuous, noninvasive, gas exchange techniques for measuring metabolic acidosis, 5) learn the mechanisms by which ventilation is controlled during exercise and how it relates to dyspnea, and 6) use the learned physiologic principles to modify therapy. Using the most advanced measurement systems available and computer technology, breath-by-breath ventilation and gas exchange measurements are made and processed to obtain a quantitative analysis of the dynamic components of gas exchange during exercise and recovery. The kinetics of respiration, circulation and metabolism in response to exercise perturbations, as well as to manipulation of factors affecting gas exchange, provide boundary conditions for the metabolic and ventilatory control mechanisms. In addition, arterial blood analyzed for PO2, PCO2, pH and metabolites which reveal the redox state of the cells define the effectiveness of the ventilatory and circulatory homeostatic mechanisms. The mechanism of the exercise hyperpnea, in man, will be studied within the frame of reference of new clues by which humoral and cardiac changes during exercise link to the ventilatory control mechanism. This project utilizes the disciplines of physiology, biochemistry and computer technology in studies on man and animals to determine the mechanisms which control the dynamics of gas exchange and ventilation during exercise, and to use this knowledge to understand pathophysiology, diagnose and treat patients with exercise limitation and dyspnea.